This proposal is designed to facilitate career development of Jeffrey Anderson, MD PhD as an independent investigator to conduct longitudinal neuroimaging studies of functional MR connectivity in neurodevelopmental and neuropsychiatric disorders, with particular expertise in functional connectivity abnormalities in autism. Although the applicant has extensive mentored research experience during PhD training in electrophysiology of the brain, and extensive neuroradiological training in functional imaging methods, he has not had experience conducting large clinical imaging investigations, requiring patient recruitment and assessment and multivariate statistical analysis of large imaging datasets. The specific research aims of this proposal develop these skills through a longitudinal study of functional connectivity in autism. There is now extensive evidence that functional connectivity abnormalities between brain regions are present in autism, which continue to develop through childhood and adolescence. These connectivity abnormalities comprise a promising technique for identifying autism subtypes, predicting prognosis, and guiding treatment. Yet the mechanism for connectivity abnormalities remains unknown. This proposal seeks to use a longitudinal investigation of functional connectivity in autism to establish whether connectivity disturbances are generalized, localized to connections of specific path length, or associated with specific functional networks. The longitudinal design will allow assessment of how these connectivity abnormalities develop through late childhood and adolescence, and will leverage the largest imaging dataset of high-functioning autism DTI and volumetric scans from late childhood to early adulthood, allowing cross-modality analysis of brain connectivity. Long term goals of the proposal are to leverage the applicant's combined training in mathematics, neuroscience, and clinical neuroimaging to build a rigorous, broad-based imaging laboratory that can make major contributions to diagnosis and understanding of neurological disorders by probing functional connectivity abnormalities in brain networks using novel imaging methods. PUBLIC HEALTH RELEVANCE: This project seeks to provide mentorship and focused research experience to provide skills necessary for him to lead cutting-edge longitudinal imaging investigations of functional connectivity in neurodevelopmental and neuropsychiatric disorders. As a primary application, a longitudinal study will be performed characterizing the mechanism and distribution of functional connectivity abnormalities in autism, yielding immense public health benefits.